The Indiana University Multipurpose Arthritis and Musculoskeletal Diseases Center (IUMAMDC) consists of a Biomedical Research Component, an Epidemiology/Education/Health Services Research (EEHSR) Component and an Administration Unit. Major biomedical research interests include the pathogenesis and treatment of osteoarthritis (OA), the causes of pain and disability in OA, and amyloidosis. Four new Developmental and Feasibility Studies are proposed in this application: one examines the reproducibility of radiographic measurement of joint space width [an issue of great relevance to the design of clinical trials of disease-modifying OA drugs (DMOADs)]; the second examines the role of arthrogenous muscle inhibition (AMI) as a cause of quadriceps weakness and a risk factor for disability, knee pain and muscle atrophy in subjects with knee OA; the third examines the use and (misuse) of magnetic resonance imaging by primary care physicians evaluating patients with low back pain; the fourth relates to inflammatory arthritis and probes the role of the receptor for platelet activating factor in cellular responses. Our EEHSR component is concerned with training of Fellows, house staff, medical students and arthritis health professionals (AHPs) and includes outreach programs and a variety of interactions with community organizations. Four new EEHSR projects are proposed, 3 of which relate to OA: the first compares the rate of tibiofemoral joint space narrowing among various subsets of subjects representing likely target populations for clinical trials of DMOADs; the second, a prospective study of patients with knee OA treated by primary care physicians in a managed care setting, compares outcomes achieved with standard care to those inpatients treated with a comprehensive program of nonpharmocologic and pharmacologic measures, graduated with respect to risk of side effects, cost and convenience. The third project builds on our observation during the current funding period that quadriceps weakness is common in community-based subjects with knee OA even in the absence of joint pain; it examines the effects of lower extremity strength training on the progression of knee pain, functional impairment and radiographic changes in the elderly. The fourth project examines the clinical and economic effects of a psychosocial intervention inpatients with recurrent acute low back pain. To support the research activities of IUMAMDC, 2 Core units are proposed: Biostatistics and Data Acquisition. Overall Center activities are supported by an Administration Unit.